Advances in the Treatment of Keloids

Keloids are a type of scar that appears firm, rubbery and nodular over an area of previous surgery, trauma, burn, acne or skin abrasion. Typically manifesting on locations where excessive tension exists during wound closure, keloids are scars that heal with an abundance of type III collagen. Over time, the scar matures and type I collagen predominates. Hypertrophic scars (HTS) are red and elevated scars characterized by prolonged chronic inflammation and excessive collagen deposition. The difference between keloids and hypertrophic scars is that while HTS can mature and improve over time, keloids rarely improve over a natural course. HTS do not extend beyond the boundaries of the original site, while keloids frequently expand beyond the original borders, extending "cheloid" clawlike projections across the skin. These keloids are often erythematous, pruritic and painful, with shiny layers of thinned epidermis stretching over the adjacent skin. Although keloids may occur anywhere, they are most commonly located on the sternum, ears, trunk, back and extremities (Figure 1). They occur less frequently on the palms or soles.

Histologically, keloids appear as fibrotic collections of excessive thick collagen bundles, elastin, fibronectin and proteoglycans along with atypical fibroblasts. The fibroblasts in keloids have increased prolyl hydroxylase activity, which is involved in collagen synthesis, at levels much higher than that of normal skin or HTS.¹ In normal scars, collagen forms regular cross-links, whereas in keloids the collagen is arranged irregularly, forming nodules in the dermis.

Epidemiologically, keloids occur more frequently in persons 10-30 years of age, with slight increase in frequency in females, presumably due to their higher frequency of ear piercing (Figure 2). Occurring with higher proportions in skin of color, keloid formation is seen in individuals of all races, with the lowest incidence in albinos. Interestingly, prevalence of keloids is correlated to skin pigmentation, with dark-skinned individuals suffering disproportionately. There is a reported incidence of 4.5-16 percent in African-American and Hispanic populations.^2,3

A specific type of keloid often affecting young African-American males is Acne Keloidalis Nuchae (AKN), a scarring alopecia in the occipital scalp and neck region caused by chronic inflammation of hair follicles.⁴ This condition is caused by repeated irritation and inward curling of coarse hairs into the epidermis, causing a foreign body granuloma and possibly autoimmune reaction, with an increase in mast cells. AKN may become secondarily infected with bacteria or yeast. This form of folliculitis often causes coalescing papules and fibrotic nodules. Of note, AKN tends to be more responsive to excision therapy, with complete removal of affected hair follicles.⁵ It may also be treated with topical steroids, immune modulators, lasers, cryotherapy, or anti-inflammatory doses of doxycycline.

A strong genetic predisposition to the formation of keloids is suggested by the increased prevalence in dark-skinned races, increased concordance among identical twins and increased familial clustering.⁶ While the mode of inheritance is not definitively known, several theories have been proposed, including autosomal recessive,⁷ autosomal dominant with incomplete penetrance⁸ and variable expression. In a familial study, 14 pedigrees with keloids spanning 3-5 generations were ob-